Abstract

Cannabis contains various cannabinoids, two of which have almost opposing
actions: Δ9-tetrahydrocannabinol (Δ9-THC) is psychotomimetic,
whereas cannabidiol (CBD) has antipsychotic effects. Hair samples were
analysed to examine levels of Δ9-THC and CBD in 140 individuals. Three
clear groups emerged: `THC only', `THC+CBD' and those with no cannabinoid in
hair. The THC only group showed higher levels of positive schizophrenia-like
symptoms compared with the no cannabinoid and THC+CBD groups, and higher
levels of delusions compared with the no cannabinoid group. This provides
evidence of the divergent properties of cannabinoids and has important
implications for research into the link between cannabis use and
psychosis.

Convergent evidence suggests a link between cannabis use and
psychosis.1 However,
cannabis comprises a combination of cannabinoids and these different
constituents may have distinct effects, not all of which are detrimental to
mental health. The main component of smoked cannabis is Δ
9-tetrahydrocannabinol (Δ9-THC), which is thought to be
responsible for the majority of the psychotomimetic effects of the drug: it
has been shown to elevate levels of anxiety and psychotic symptoms in healthy
individuals.2 In
contrast, cannabidiol (CBD), another major constituent of some strains of
cannabis, has been found to be anxiolytic and to have antipsychotic
properties,3,4
and may be neuroprotective in
humans.5 The ratio
of these two compounds in smoked cannabis varies – there are higher
levels of Δ9-THC in `skunk' or genetically modified strains of the
plant.6 Cannabis
users are often unaware of the ratio of CBD to Δ9-THC because CBD has no
psychotomimetic effect in
humans.3 Elevated
levels of psychosis proneness and delusions have been found in people who use
cannabis regularly.7
Despite suggestions about the different psychological properties of these two
constituents of smoked cannabis, no prior research has examined the link
between psychosis proneness and delusions and the CBD/Δ9-THC ratio in
those who use cannabis. This study aimed to use hair analytic techniques to
examine levels of Δ9-THC and CBD, and relate these objective indices of
cannabis use to measures of psychosis proneness and delusional thinking.

Method

Our sample consisted of 140 individuals who were taking part in an ongoing
longitudinal study,8
which involved groups categorised as current and former ketamine users, other
drug users and non-users. Inspection of the hair analysis results from the
sample revealed that 54 individuals screened positive for cannabis.
Confirmatory screens showed both CBD and Δ9-THC in the hair of 26 of
these individuals but Δ9-THC alone in the hair of 20 others. Only
individuals who showed evidence of Δ9-THC–carboxylic acid in hair
as well as Δ9-THC were included, because this indicated actual
consumption rather than passive use. The remaining 8 people who screened
positive showed evidence of CBD alone in their hair samples, but they were
excluded from this study as the group size was too small for statistical
analysis. Rather than correlating the exact levels of CBD and Δ9-THC
with symptoms – as concentrations have been shown to be vulnerable to
other factors (e.g. hair washing or
dyeing)9 – we
divided the sample into three groups: those with Δ9-THC only in hair
(`THC only': n=20; mean age 26.1 years, s.d.=6.21; 13 males); those
with Δ9-THC and CBD in hair (`THC+CBD': n=27; mean age 27.8
years, s.d.=6.26; 21 males); and those with no cannabinoids in hair
(n=85; mean age 26.7 years, s.d.=6.59; 58 males).

Hair analysis was performed by gas chromatography/mass spectrometry
(GC/MS). Following addition of THC-d3 (Tricho-Tech, UK;
www.tricho-tech.co.uk)
as the internal standard, 50 mg of the powdered hair was dissolved in 1 ml of
0.1 mol/l sodium hydroxide (100°C for 30 min). The solution was adjusted
to a pH of 5.5 with 1.0 mol/l hydrochloric acid, and the Δ9-THC and CBD
were extracted into n-hexane and quantified by GC/MS after silyation.
The lower limit of detection was 0.025 ng/mg for both Δ9-THC and
CBD.

The short form of the Oxford Liverpool Inventory of Life Experiences
(OLIFE) questionnaire was used to assess psychosis
proneness.10 This
measure yields four factors: unusual experiences (an analogue of positive
symptoms in schizophrenia, including hallucinations and delusions); cognitive
disorganisation (roughly corresponding to thought disorder); introvertive
anhedonia (negative symptoms such as social withdrawal); and impulsive
non-conformity (relates to behavioural impulsivity).

Peter's Delusion Inventory (PDI) was used to index delusional
thinking.11

Results

One-way analysis of variance (ANOVA) showed that there was no significant
difference in age or in drug use (other than cannabis) reported in the three
groups. Chi-squared tests revealed no difference in gender. The mean CBD level
in the THC+CBD group was 0.15 ng/mg (s.d.=0.27). A Mann–Whitney
U-test (as variance was heterogeneous) found no significant
difference in the mean level of Δ9-THC in the THC only group (0.17
ng/mg, s.d.=0.07) and the THC+CBD group (0.19 ng/mg, s.d.=0.33).

Subjective estimates of cannabis use in these two groups did not differ in
days per month of use (THC only, mean=19.4 days, s.d.=10.0; THC+CBD, mean=21.1
days, s.d.=10.1); age at which the participant became a regular user (THC
only, mean=16.5 years, s.d.=3.07; THC+CBD, mean=5.48 years, s.d.=4.69) or days
since last use (THC only, mean=3.89 days, s.d.=8.56; THC + CBD, mean=2.67
days, s.d.=3.96). There was a significant difference in number of days taken
to smoke 3.5 g of cannabis (the standard quantity in which cannabis is sold in
the UK, used as a more reliable indicator than amount smoked per session),
with the THC only group taking longer (mean=10.2 days, s.d.=8.61) to smoke 3.5
g than the THC+CBD group (mean=5.0 days, s.d.=6.03);
F(1,46)=5.59, P=0.023. Subjective estimates of
cannabis use were not correlated with levels of Δ9-THC and CBD obtained
from hair analysis.

Psychosis proneness

One-way ANOVA yielded significant differences between the three groups in
scores on the OLIFE factor of unusual experiences:
F(2,129)=12.86, P<0.001
(Fig. 1). Post hoc Scheffe's
test showed that this was due to greater scores in the THC only group compared
with the no cannabinoid group (P<0.001) and the THC+CBD group
(P=0.021). Significant differences also emerged for the factor of
introvertive anhedonia (F(2,129)=7.45, P=0.001),
with significantly lower scores in the THC+CBD group compared with the no
cannabinoid group (P=0.001) and the THC only group
(P=0.035).

Delusional thinking

One-way ANOVA revealed significant group differences in scores on the PDI:
F(2,129)=5.90, P=0.004. Compared with the no
cannabinoid group (mean score 5.48, s.d.=3.58) there were significantly higher
scores in the THC only group (mean score 8.15, s.d.=3.16; P=0.012)
and a trend for greater scores in the THC+CBD group (mean score 7.22,
s.d.=3.23; P=0.088).

Discussion

Our results show higher levels of unusual experiences – an analogue
of hallucinations and delusions – in individuals who had evidence of
only Δ9-THC in their hair compared with those with both Δ9-THC and
CBD, and those with no cannabinoid. There were also greater levels of
delusions in this THC only group compared with individuals who showed no
evidence of cannabinoids in their hair, with a similar trend in the THC+CBD
group. The THC+CBD group reported less anhedonia than the other two groups.
This study is the first to demonstrate that hair analytic techniques can be
used to define subsets of cannabis users. The implications of these findings
are that people who smoke different strains of cannabis manifest different
psychological symptoms.

These preliminary findings may support previous work showing the
antipsychotic properties of CBD in the
laboratory.3,4
Moreover, this suggests that smoking strains of cannabis containing CBD in
addition to Δ9-THC may be protective against the psychotic-like symptoms
induced by Δ9-THC alone. This is further evident from the findings that
participants with both Δ9-THC and CBD in their hair had significantly
less anhedonia than the other groups in this study. However, another potential
explanation of the results of our study is that pre-existing differences in
psychosis proneness between people who use cannabis may draw them to smoke
different strains of the drug. In spite of this, the former explanation seems
more plausible in light of the absence of differences in any other
recreational drug use between these groups, and the emerging evidence of
neuroprotective effects of CBD. A further limitation of this research is that
the mechanisms by which cannabinoids are incorporated into hair are not well
understood, and thus we cannot directly infer the ratio of CBD to Δ
9-THC. Despite this, our study highlights the importance of
distinguishing between different cannabinoids and has implications in the
debate over the link between cannabis use and psychosis.

Acknowledgments

H.V.C. and C.J.A.M. were supported by a grant from the Economic and Social
Research Council (RES-000-23-0945).